1. Technical Field
This document relates to methods and materials for detecting C9ORF72 hexanucleotide (GGGGCC) (SEQ ID NO: 3) repeat expansion positive (C9+) frontotemporal lobar degeneration (FTLD) or C9+ amyotrophic lateral sclerosis (ALS). For example, this document provides methods and materials related to using anti-(GP)8 (SEQ ID NO: 2) antibodies to identify mammals (e.g., humans) having C9+ FTLD or C9+ ALS.
2. Background Information
FTD and ALS are both devastating neurological diseases. FTD is the second most common cause of pre-senile dementia in which degeneration of the frontal and temporal lobes of the brain results in progressive changes in personality, behavior, and language with relative preservation of perception and memory (Graff-Radford and Woodruff, Neurol., 27:48-57 (2007)). ALS affects 2 in 100,000 people and has traditionally been considered a disorder in which degeneration of upper and lower motor neurons gives rise to progressive spasticity, muscle wasting, and weakness. However, ALS is increasingly recognized to be a multisystem disorder with impairment of frontotemporal functions such as cognition and behavior in up to 50% of patients (Giordana et al., Neurol. Sci., 32:9-16 (2011); Lomen-Hoerth et al., Neurology, 59:1077-1079 (2003); and Phukan et al., Lancet Neurol., 6:994-1003 (2007)). Similarly, as many as half of FTD patients develop clinical symptoms of motor neuron dysfunction (Lomen-Hoerth et al., Neurology, 60:1094-1097 (2002)). The concept that FTD and ALS represent a clinicopathological spectrum of disease is strongly supported by the recent discovery of the transactive response DNA binding protein with a molecular weight of 43 kD (TDP-43) as the pathological protein in the vast majority of ALS cases and in the most common pathological subtype of FTD (Neumann et al., Science, 314:130-133 (2006)), now referred to as frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP; Mackenzie et al., Acta Neuropathol., 117:15-18 (2009)).